Authors: María Jimena Salcedo-Arellano, MD, Jun Yi Wang, PhD, Yingratana A. McLennan, BS, Mai Doan, BS, Ana Maria Cabal-Herrera, MD, Sara Jimenez, BS, Marisol W. Wolf-Ochoa, BS, Desiree Sanchez, BS, Pablo Juarez, BS, Flora Tassone, PhD, Blythe Durbin-Johnson, PhD, Randi J. Hagerman, MD, and Verónica Martínez-Cerdeño, PhD (Journal Name, Volume, page#)

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Abstract: Fragile X–associated tremor/ ataxia syndrome is a neurodegenerative disease of late onset developed by carriers of the premutation in the fragile x mental retardation 1 (FMR1) gene. Pathological fea- tures of neurodegeneration in fragile X–associated tremor/ ataxia syndrome include toxic levels of FMR1 mRNA, ubiquitin-positive intranuclear inclusions, white matter dis- ease, iron accumulation, and a proinflammatory state. Objective: The objective of this study was to analyze the presence of cerebral microbleeds in the brains of patients with fragile X–associated tremor/ataxia syndrome and investigate plausible causes for cerebral microbleeds in fragile X–associated tremor/ataxia syndrome.

Methods: We collected cerebral and cerebellar tissue from 15 fragile X–associated tremor/ataxia syndrome cases and 15 control cases carrying FMR1 normal alleles. We performed hematoxylin and eosin, Perls and Congo red stains, ubiquitin, and amyloid β protein immunostaining. We quantified the number of cerebral

microbleeds, amount of iron, presence of amyloid β within the capillaries, and number of endothelial cells containing intranuclear inclusions. We evaluated the relationships between pathological findings using correlation analysis.

Results: We found intranuclear inclusions in the endo- thelial cells of capillaries and an increased number of cerebral microbleeds in the brains of those with fragile X–associated tremor/ataxia syndrome, both of which are indicators of cerebrovascular dysfunction. We also found a suggestive association between the amount of capil- laries that contain amyloid β in the cerebral cortex and the rate of disease progression.

Conclusion: We propose microangiopathy as a patho- logic feature of fragile X–associated tremor/ataxia syndrome. © 2021 International Parkinson and Movement Disorder Society

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Authors: Sarwat Amina, Carmen Falcone , Tiffany Hong, Marisol Wendy Wolf-Ochoa, Gelareh Vakilzadeh, Erik Allen, Rosalia Perez-Castro, Maryam Kargar, Stephen Noctor and Verónica Martínez-Cerdeño

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Abstract: An alteration in the balance of excitation-inhibition has been proposed as a common characteristic of the cerebral cortex in autism, which may be due to an alteration in the number and/or function of the excitatory and/or inhibitory cells that form the cortical circuitry. We previously found a decreased number of the parvalbumin (PV)+ interneuron known as Chandelier (Ch) cell in the prefrontal cortex in autism. This decrease could result from a decreased number of Ch cells, but also from decreased PV protein expression by Ch cells. To further determine if Ch cell number is altered in autism, we quantified the number of Ch cells following a different approach and different patient cohort than in our previous studies. We quantified the number of Ch cell cartridges—rather than Ch cell somata—that expressed GAT1—rather than PV. Specifically, we quantified GAT1+ cartridges in prefrontal areas BA9, BA46, and BA47 of 11 cases with autism and 11 control cases. We found that the density of GAT1+ cartridges was decreased in autism in all areas and layers. Whether this alteration is cause or effect remains unclear but could result from alterations that take place during cortical prenatal and/or postnatal development.

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